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  • Title: Binding characteristics and tumor targeting of a covalently linked divalent CC49 single-chain antibody.
    Author: Beresford GW, Pavlinkova G, Booth BJ, Batra SK, Colcher D.
    Journal: Int J Cancer; 1999 Jun 11; 81(6):911-7. PubMed ID: 10362138.
    Abstract:
    Multivalency is a recognized means of increasing the functional affinity of single-chain Fvs (scFvs) for optimizing tumor uptake. A unique divalent single-chain Fv protein [sc(Fv)2], based on the variable regions of the monoclonal antibody (MAb) CC49, has been generated that differs from other dimeric single-chain constructs in that a linker sequence (L) is encoded between the repeated V(L) and V(H) domains (V(L)-L-V(H)-L-V(L)-L-V(H)). This construct was expressed in soluble form in Escherichia coli and purified by ion-exchange and gel-filtration chromatography. Purity and immunoreactivity were determined by SDS-PAGE, HPLC and competitive RIA. sc(Fv)2 exhibited a relative K(A) (3.34 x 10(7) M(-1)) similar to that of the native IgG (1.14 x 10(8) M(-1)) as determined by BIAcore analysis. Pharmacokinetic studies showed rapid blood clearance for sc(Fv)2, with a T(1/2) less than 40 min. Whole-body clearance analysis also revealed rapid clearance, suggesting no significant retention in the extravascular space or normal tissues. Biodistribution studies of radiolabeled sc(Fv)2 showed tumor uptake greater than 6% ID/g after 30 min, which remained at this level for 6 hr. High tumor uptake and retention of sc(Fv)2 coupled with rapid blood and whole-body clearance makes this dimeric scFv of MAb CC49 a strong candidate for imaging and therapeutic applications.
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